Tissue characterization based on impedance images and on impedance measurements

ABSTRACT

Apparatus for aiding in the identification of tissue type for an anomalous tissue in an impedance image comprising:  
     means for providing an polychromic immitance map of a portion of the body;  
     means for determining a plurality of polychromic measures from one or both of a portion of the body; and  
     a display which displays an indication based on said plurality of polychromic measures.

CROSS REFERENCE TO RELATED APPLICATION

[0001] This application is a Continuation-in-Part of InternationalApplication No. PCT/US95/06141, filed May 19, 1995, the disclosure ofwhich is incorporated by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present invention relates to systems for tissuecharacterization based on impedance measurement at a point or at anarray of points.

BACKGROUND OF THE INVENTION

[0003] The measurement of electrical potentials on the skin has manyuses. For example, electrocardiograms are derived from measuring thepotential generated by the heart of a patient at various points on theskin.

[0004] Skin potentials are also measured in apparatus for determiningthe electrical impedance of human tissue, including two-dimensional(e.g., U.S. Pat. Nos. 5,063,937, 4,291,708 and 4,458,694) orthree-dimensional (e.g., U.S. Pat. Nos. 4,617,939 and 4,539,640) mappingof the tissue impedance of the body. In such systems an electricalpotential is introduced at a point or points on the body and measured atother points at the body. Based on these measurements and on algorithmswhich have been developed over the past several decades, an impedancemap or other indication of variations in impedance can be generated.

[0005] U.S. Pat. Nos. 4,291,708 and 4,458,694 and “Breast Cancerscreening by impedance measurements” by G. Piperno et al. Frontiers Med.Biol. Eng., Vol. 2, pp 111-117, the disclosures of which areincorporated herein by reference, describe systems in which theimpedance between a point on the surface of the skin and some referencepoint on the body of a patient is determined. These references describethe use of a multi-element probe for the detection of cancer, especiallybreast cancer, utilizing detected variations of impedance in the breast.

[0006] In these references a multi-element probe is described in which aseries of flat, stainless steel, sensing elements are mounted onto a PVCbase. A lead wire is connected between each of these elements anddetector circuitry. Based on the impedance measured between the elementsand a remote part of the body, signal processing circuitry determinesthe impedance variations in the breast. Based on the impedancedetermination, tumors, and especially malignant tumors, can be detected.

[0007] The multi-element probe is a critical component in this systemand in other systems which use such probes. On one hand the individualelements must make good contact with the skin and with the correspondingpoints on the sensing or processing electronics while also being wellisolated from each other. On the other hand, use of gels to improve skincontact carries the risk of cross-talk, dried gel build-up on theelements and inter-patient hygienic concerns.

[0008] A paper titled “Capacitive Sensors for In-Vivo Measurements ofthe Dielectric Properties of Biological materials” by Karunayake P. A.P. Esselle and Stanislaw S. Stuchly (IEEE Trans. Inst & Meas. Vol. 37,No. 1, p. 101-105) describes a single element probe for the measurementof in vivo and in vitro measurements of the dielectric properties ofbiological substances at radio and microwave frequencies. The sensorwhich is described is not suitable for impedance imaging.

[0009] A paper entitled “Messung der elektrischen Impedance vonorganen—Apparative Ausrüstung für Forschung und klinishe Anwendung” byE. Gersing (Biomed. Technik 36 (1991), 6-11) describes a system whichuses single element impedance probes for the measurement of theimpedance of an organ. The device described is not suitable forimpedance imaging.

[0010] A Paper titled “MESURE DE L'IMPEDANCE DES TISSUS HEPATIQUELESTRANSFORMES PAS DES PROCESSUS LESIONELS” by J. Vrana et al. (Ann.Gastroentreol. Hepetol., 1992, 28, no. 4, 165-168) describes a probe forassessing deep tissue by use of a thin injection electrode. Theelectrode was positioned by ultrasound and specimens were taken forcytological and histological assessment. The electrode was constitutedon a biopsy needle used to take the samples.

[0011] A paper titled “Continuous impedance monitoring during CT-guidedstereotactic surgery: relative value in cystic and solid lesions” by V.Rajshekhar (British Journal of Neurosurgery (1992) 6, 439-444) describesusing an impedance probe having a single electrode to measure theimpedance characteristics of lesions. The objective of the study was touse the measurements made in the lesions to determine the extent of thelesions and to localize the lesions more accurately. The probe is guidedto the tumor by CT and four measurements were made within the lesion asthe probe passed through the lesion. A biopsy of the lesion wasperformed using the outer sheath of the probe as a guide to position,after the probe itself was withdrawn.

[0012] A paper titled “Rigid and Flexible Thin-Film Multi-electrodeArrays for Transmural Cardiac Recording” by J. J. Mastrototaro et al.(IEEE TRANS. BIOMED. ENG. Vol. 39, No. 3, March 1992, 271-279) describesa needle probe and a flat probe each having a plurality of electrodesfor the measurement of electrical signals generated in the heart.

[0013] A paper entitled “Image-Based Display of Activation PatternsDerived from Scattered Electrodes” by D. S. Buckles et al. (IEEE TRANS.BIOMED ENGR. Vol. 42, No. 1, January 1995, 111-115) describes a systemfor measurement of electrical signals generated on the heart by use ofan array of electrodes on a substrate. The heart with the electrodes inplace is viewed by a TV camera and an operator marks the positions ofthe electrodes on a display. The system then displays the heart (asvisualized prior to the placement of the electrodes) with the positionmarkings.

[0014] A paper entitled “Development of a Multiple Thin-Film SemimicroDC-Probe for Intracerebral Recordings” by G. A. Urban et al. (IEEETRANS. BIOMED ENGR. Vol. 37, No. 10, October 1990, 913-917) describes anelongate alumina ceramic probe having a series of electrodes along itslength and circumference for measuring functional parameters (electricalsignals) in the brain. Electrophysiological recording, together withelectrostimulation at the target point during stereotactic surgery, wasperformed in order to ensure exact positioning of the probe afterstereotactic calculation of the target point. Bidimensional X-Rayimaging was used in order to verify the exact positioning of theelectrode tip.

SUMMARY OF THE INVENTION

[0015] It is an object of certain aspects of the invention to provide amulti-element probe having improved and more uniform and repeatablecontact with the skin with minimal operator expertise and minimal riskof cross-patient contamination.

[0016] It is an object of certain aspects of the invention to provideimproved inter-element electrical isolation, and to permit sliding ofthe probe while it is urged against the skin.

[0017] It is an object of certain aspects of the invention to provide arelatively inexpensive disposable multi-element probe.

[0018] It is an object of certain aspects of the invention to provide amulti-element probe having sufficient transparency to allow for viewingof tissue surface features and to allow for referencing the probe withrespect to physical features of or on the skin.

[0019] It is an object of certain aspects of the invention to provide amethod of distinguishing between artifacts and abnormalities.

[0020] It is an object of certain aspects of the invention to provide asystem for electrical impedance imaging which simultaneously acquires,uses and preferably displays both capacitance and conductanceinformation.

[0021] It is an object of certain aspects of the invention to provide asystem for electrical impedance testing of the breast or other bodyregion which provides more accurate information regarding the positionof impedance abnormalities detected in the breast or other region.

[0022] It is an object of certain aspects of the invention to providefor electrical impedance testing with a variable spatial resolution.

[0023] It is an object of certain aspects of the invention to providefor two dimensional electrical impedance testing giving an indication ofthe distance of an abnormality from the surface of the skin.

[0024] It is an object of certain aspects of the invention to provideapparatus especially suitable for breast impedance measurements.

[0025] It is an object of certain aspects of the invention to provideguidance for placement of elongate objects such as biopsy needles,localization needles, fiber optic endoscopes and the like using realtime and/or recorded stereotactic images to guide the object.

[0026] It is a further object of certain aspects of the invention toprovide a biopsy needle having an impedance measuring function to aid inthe taking of a biopsy.

[0027] It is an object of certain aspects of the invention to providemore direct comparison between the results of electrical impedance mapsand the results of optical, ultrasound or other imaging modalities.

[0028] It is an object of certain aspects of the invention to provideapparatus and method for indicating, on an anatomical illustration, thelocation and region from which an impedance image, shown together withthe illustration is derived.

[0029] It is an object of certain aspects of the invention to provideapparatus which facilitates direct comparison between X-Ray andimpedance mammographic images, as for example by superposition of theimages.

[0030] It is an object of certain aspects of the invention to provide amethod of determining a polychromic (multi-frequency) impedance map.

[0031] It is an object of certain aspects of the invention to optimizethe impedance mapping utilizing a pulsed voltage excitation.

[0032] It is an object of certain aspects of the invention to providepalpation and tactile sensing of an area while simultaneously providingan impedance image of the area.

[0033] It is an object of certain aspects of the invention to allow forthe identification of tissue types from impedance maps.

[0034] In general, the term “skin” as used herein means the skin orother tissue of a subject.

[0035] The present inventor has found that when, in an impedance image,an anomaly is perceived, the type of tissue underlying the position ofthe anomaly on the image may generally be determined by acharacterization procedure which includes the determination of a numberof polychromic measures for the anomaly and surrounding non-anomaloustissue and comparison of the measures with ranges of values ofindividual polychromic measures or their combinations which arecharacteristic of various types of tissue. It has been found that normaltissue such as breast tissue, nipples and the infra-mammary ridge, ribsand Costo-chondral Junctions and benign hyperplasia can generally bedistinguished from cancerous tumors and precancerous atypicalhyperplasia. These measures are based on the structure and form of thedeviation of the capacitance and conductance of the anomalous portion ofthe image from that of the surrounding, normal tissue. For those caseswhere there is some ambiguity between some types of tissue, knowledge ofthe anatomy of the imaged area or palpation of the area can often removethe ambiguity or additional views can be taken to remove the ambiguity.

[0036] In an image the measures are preferably determined by comparingthe capacitance or conductance of the anomalous pixels on the image tobe characterized with the capacitance or conductance of normative tissuearound the mean or median value of the capacitance or conductance,typically in terms of quantified deviation of a given pixel or regionfrom the median in the image, as measured in multiples of the estimatedstandard deviation or coefficient of variance.

[0037] The method is also potentially useful to determine tissue typesin situations where either a single impedance probe is used or where theimage is small and only anomalous areas are imaged. In these cases thecomparison is made between the values of capacitance or conductancemeasured for the anomalous region as compared to the capacitance orconductance measured for a nearby region known to be normal.

[0038] As used herein the term immitance means either the complexadmittance or impedance. Furthermore the term polychromic measure is ameasure which is based on the immitance or on the real or imaginary partthereof or on a combination of the immitance and/or the real partthereof and/or the imaginary part thereof at a plurality of frequencies,i.e., on the spectrum thereof.

[0039] There is therefore provided, in accordance with a preferredembodiment of the invention apparatus for aiding in the identificationof tissue type for an anomalous tissue in an impedance image comprising:

[0040] means for providing an polychromic immitance map of a portion ofthe body;

[0041] means for determining a plurality of polychromicmeasures,-preferably normalized measures, of an anomalous region of theimmitance image; and

[0042] a display which displays an indication based on said plurality ofpolychromic measures.

[0043] Preferably the apparatus includes means for providing a map ofsaid polychromic measures and wherein said indication includes a displayof a plurality of said maps.

[0044] In a preferred embodiment of the invention the display includesan overlay of maps of said polychromic measures.

[0045] Preferably the apparatus includes means for matching the valuesof the plurality of measures with predetermined values of the measuresto identify the tissue type of the anomalous tissue.

[0046] In one preferred embodiment of the invention the indication isthe display of a map of said determined tissue type.

[0047] There is further provided, in accordance with a preferredembodiment of the invention, apparatus for determining a tissue type foran anomalous tissue comprising:

[0048] means for determining a plurality of polychromic measures of theanomalous tissue; and

[0049] means for matching the values of the plurality of measures withpredetermined values of the measures to identify the tissue type of theanomalous tissue.

[0050] There is further provided, in accordance with a preferredembodiment of the invention, a method of determining a tissue type fortissue in an anomalous region in an immitance image, comprising:

[0051] determining a plurality of polychromic measures, preferablynormalized measures, of said anomalous region; and

[0052] matching the values of the plurality of measures to identify thetissue type of the anomalous region.

[0053] There is further provided, in accordance with a preferredembodiment of the invention, a method of determining a tissue type foran anomalous tissue:

[0054] determining a plurality of polychromic measures, preferablynormalized measures, of the anomalous tissue;

[0055] matching the values of the plurality of measures withpredetermined values to identify the tissue type of the anomaloustissue.

[0056] Preferably, one of the polychromic measures is derived from thesum, over a plurality of frequencies, of the positive deviations of thecapacitance of the anomaly from that of typical nonanomolous regions.

[0057] Preferably, one of the polychromic measures is derived from thesum, over a plurality of frequencies, of the negative deviations of thecapacitance of the anomaly from that of typical nonanomolous regions.

[0058] Preferably, one of the polychromic measures is derived from thesum, over a plurality of frequencies, of the positive deviations of theconductance of the anomaly from that of typical nonanomolous regions.

[0059] Preferably one of the measures is the integral of the phase orthe sum of phase values over a range of frequencies.

[0060] Preferably, one of the measures is the difference between theintegral of the difference between the phase at a point and the mean ormedian value of the phase in the image, over a range of frequencies.

[0061] Preferably, one of the measures is the derivative of thecapacitance curve or its logarithm as a function of frequency, evaluatedat a given frequency.

[0062] Preferably, one of the measures is the derivative of theconductance curve or its logarithm as a function of frequency, evaluatedat a given frequency.

[0063] Preferably, one of the measures is a frequency at which the phaseof the impedance reaches a specified value, preferably 45 degrees.

BRIEF DESCRIPTION OF THE DRAWINGS

[0064] The invention will be more fully understood and appreciated fromthe following detailed description, taken in conjunction with thedrawings in which:

[0065]FIG. 1 is an overall view of an impedance mapping systemespecially suitable for breast impedance mapping in accordance with apreferred embodiment of the invention;

[0066]FIG. 2 is a perspective view of an imaging head suitable forbreast impedance mapping in accordance with a preferred embodiment ofthe invention;

[0067]FIGS. 3A and 3B show partially expanded views of two preferredprobe head configurations suitable for use in the imaging head of FIG.2;

[0068]FIG. 4 is a top view of a portion of a multi-element probe inaccordance with a preferred embodiment of the invention;

[0069]FIG. 5A is a partial, partially expanded cross-sectional side viewof the probe of FIG. 4 along lines V-V, suitable for the probe headconfiguration of FIG. 3B;

[0070]FIG. 5B is a partially expanded cross-sectional side view of analternative probe in accordance with a preferred embodiment of theinvention;

[0071]FIG. 5C shows an alternative embodiment of a multi-element probe,in accordance with a preferred embodiment of the invention;

[0072]FIG. 6A is a perspective view of a hand held probe in accordancewith a preferred embodiment of the invention;

[0073]FIG. 6B shows a partially expanded bottom view of the probe ofFIG. 6A, in accordance with a preferred embodiment of the invention;

[0074]FIG. 7A is a perspective view of a fingertip probe in accordancewith a preferred embodiment of the invention;

[0075]FIG. 7B shows a conformal multi-element probe;

[0076]FIG. 8 shows an intra-operative probe used determining theposition of an abnormality in accordance with a preferred embodiment ofthe invention;

[0077]FIG. 9 shows a laparoscopic probe in accordance with a preferredembodiment of the invention;

[0078]FIG. 10 shows a biopsy needle in accordance with a preferredembodiment of the invention;

[0079]FIG. 11A illustrates a method of using the biopsy needle of FIG.10, in accordance with a preferred embodiment of the invention;

[0080]FIG. 11B illustrates a portion of a display used in conjunctionwith the method of FIG. 11A;

[0081]FIG. 11C shows a biopsy guiding system in accordance with apreferred embodiment of the invention;

[0082]FIG. 11D shows a frontal biopsy guiding system in accordance witha preferred embodiment of the invention;

[0083]FIG. 11E shows a lateral biopsy guiding system in accordance witha preferred embodiment of the invention;

[0084]FIG. 12 shows, very schematically, the inter-operative probe ofFIG. 8 combined with a video camera use to more effectively correlate animpedance measurement with placement of the probe.

[0085]FIG. 13 illustrates a laparoscopic probe according to theinvention used in conjunction with a fiber-optic illuminator-imager;

[0086]FIG. 14 illustrates a display, according to a preferred embodimentof the invention showing both capacitive and conductance imagesillustrative of atypical hyperplasia;

[0087]FIG. 15 illustrates a display, according to a preferred embodimentof the invention showing both capacitive and conductance imagesillustrative of a carcinoma;

[0088]FIG. 16 illustrates a method useful for verifying a detected localimpedance deviation as being non-artifactal and for estimating thedeviation;

[0089]FIGS. 17A and 17B are a block diagram of circuitry suitable forimpedance mapping in accordance with a preferred embodiment of theinvention; and

[0090] FIGS. 18A-18C show maps of polychromic measures characteristic ofcertain tissue types.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0091] Reference is made to FIGS. 1 and 2 which illustrate an impedancemapping device 10 suitable for mapping the impedance of a breast.

[0092] Mapping device 10 includes an imaging head 12, which is describedbelow, which holds the breast and provides contact therewith forproviding electrical excitation signals thereto and for receivingresultant electrical signals therefrom. Signals to and from the head aregenerated and received by a computer/controller 14 which producesimpedance maps of the breast under test for display on a monitor 16. Theimpedance maps may be stored in computer/controller 14 for later viewingor processing or hard copies may be provided by a hard copy device 18which may be a laser printer, video printer, Polaroid or film imager ormulti-imager.

[0093] The entire mapping device 10 may be conveniently mounted on adolly 20 to facilitate placement of the imaging head with respect to thepatient.

[0094]FIG. 1 also shows a hand held probe 100, described in more detailbelow, and a reference probe 13.

[0095]FIG. 2 shows imaging head 12 in more detail. Head 12 comprises amovable lower plate probe 22 and a stationary upper plate probe 24 whichis mounted on a pair of rails 26 to allow the distance between plateprobes 22 and 24 to be varied.

[0096] Movement of plate probe 22 along rails 26 may be achieved eitherby a motor (not shown) including suitable protection againstover-pressure as is traditional in X-ray breast imaging, or by hand.

[0097] Either or both of plate probes 22 and 24 are provided withmulti-element probes 28 and 30 respectively, which are described morefully below, which electrically contact the breast with a plurality ofsensing elements to optionally provide electrical excitation to thebreast and to measure signals generated in response to the providedsignals. Alternatively, electrical excitation to the breast is providedby reference probe 13 which is placed on the arm, shoulder or back ofthe patient, or other portion of the patient.

[0098] In practice, a breast is inserted between probes 28 and 30 andplate probe 24 is lowered to compress the breast between the probes.This compression reduces the distance between the probes and providesbetter contact between the sensing elements and the skin of the breast.Although compression of the breast is desirable, the degree ofcompression required for impedance imaging is much lower than for X-Raymammography, and the mapping technique of the present invention istypically not painful.

[0099] Alternatively or additionally, the probes are curved to conformwith the surface of the breast.

[0100] Head 12 is provided with a a pivot (not shown) to allow forarbitrary rotation of the head about one or more of its axes. Thisallows for both medio-lateral and cranio-caudal maps of the breast to beacquired, at any angular orientation about the breast. Preferably, head12 may be tilted so that the surfaces of plate probes 22 and 24 areoriented with a substantial vertical component so that gravity assiststhe entry of the breast into the space between the maximum extent and tokeep it from inadvertently falling out. This is especially useful whenthe patient leans over the plates so that her breasts are positioneddownwardly between the plate probes.

[0101] Furthermore, in a preferred embodiment of the invention, one orboth of probes 28 and 30 may be rotated about an axis at one endthereof, by a rotation mechanism 27 on their associated plate probes 22or 24, such as is shown in FIG. 2 for probe 28. Additionally oralternatively, probes 28 and/or 30 may be slidable, as for example alongmembers 31.

[0102] Such additional sliding and rotating flexibility is useful forproviding more intimate skin contact of the probes with the breast,which has a generally conical shape. Furthermore, such flexibilityallows for better imaging of the areas of the breast near the chest wallor the rib cage, which are extremely difficult to image in x-raymammography.

[0103]FIGS. 3A and 3B show partially expanded views of two probe headconfigurations suitable for use in the imaging head of FIG. 2, inaccordance with preferred embodiments of the invention.

[0104] In the embodiment of FIG. 3A, a preferably removablemulti-element probe 62, which is described below in more detail, isattached to a probe head base 50 via a pair of mating multi-pinconnectors 51 and 52. A cable 53 couples connector 52 to computer 14.When multi-element probe 62 is inserted into base 50 (that is to say,when connector 51 is fully inserted into connector 52), the relativelystiff bottom of probe 62 rests on ledges 54 formed in the base, suchthat the surface 55 of the base and the surface of element 62 arepreferably substantially coplanar.

[0105] In the embodiment of FIG. 3B, a series of contacts 82 are formedon base 50 and a disposable multi-element probe 62′ is attached to thecontacts as described below with reference to FIG. 5A and 5B. Cable 53couples the contacts to computer 14.

[0106]FIGS. 4, 5A and 5B show top and side views of a portion ofmulti-element probe 62′ and contacts 74, while FIGS. 5A and 5B show apartially expanded cross-sectional side view of probe 62′ along linesV-V. While the embodiment shown in FIGS. 4, 5A and 5B is especiallysuitable for the probe head configuration of FIG. 3B, much of thestructure shown in these FIGS. 5 is common to multi-element probes usedin other configurations described herein.

[0107] As shown in FIGS. 4, 5A and 5B, disposable multi-element probe62′ preferably incorporates a plurality of sensing elements 64,separated by separator or divider elements 66.

[0108] As shown more clearly in FIGS. 5A and 5B, sensing elements 64,comprise a bio-compatible conductive material (for example NeptrodeE0751 or Neptrode E0962 Hydrogel distributed by Cambrex Hydrogels,Harriman, N.Y.) such as is sometimes used for ECG probes in a well 70formed by a first, front, side of a mylar or other flexible,non-conducting substrate 68, such as a thin mylar sheet and the dividerelements 66. A suitable thickness for the mylar sheet is approximately0.2 mm for probe 62′. The substrate is preferably pierced in the centerof each well. The hole resulting from the piercing is filled with aconducting material which is also present on the bottom of well 70 andon a second, back, side of substrate 68 to form a pair of electricalcontacts 72 and 74 on either side of the substrate and an electricallyconducting feed-through 76 between the pair of contacts. As shown, aseparate contact pair and feed-through is provided for each sensingelement.

[0109] Alternatively, the substrate may be formed of any suitable inertmaterial including plastics such as polyethylene, polypropylene, PVC,etc.

[0110] Wells 70 may be formed in a number of ways. One method of formingthe wells is to punch an array of square holes in a sheet of plastic,such as polypropylene, which is about 0.2-1 mm thick. This results in asheet containing only the divider elements. This sheet is bonded tosubstrate 68 which has been pre-pierced and in which the contacts andfeed-throughs have been formed. Another method of forming the wells isto emboss a substrate containing the contacts and feed-throughs to formdivider elements in the form of ridges which protrude from the substrateas shown in FIG. 5B. Yet another method of producing the wells is byprinting the well walls using latex based ink or other bio-compatiblematerial having a suitable firmness and flexibility. Another method ofproduction is by injection molding of the substrate together with thedivider elements. And yet another method of producing the wells is bylaminating to the substrate a preformed grid made by die cutting thearray of divider elements in a sheet of plastic, injection molding, orother means.

[0111] The conductors and feed-throughs may be of any conductivematerial which will provide reliable feed-through plating of the holes.One method of manufacturing the contacts and holes is by screen printingof the contacts on both sides of the substrate. If conductive pastehaving a suitable viscosity is used, the paste will fill the hole andform a reliable contact between contacts 72 and 74. Although manyconductive materials can be used, non-polarizing conductors, such assilver/silver chloride are preferred. A conductive paste suitable forsilk screening the conductors onto the substrate is Pad PrintableElectrically conductive Ink No. 113-37 manufactured and sold by CreativeMaterials Inc., Tyngsboro, Mass.

[0112] In general contacts 72 and 74 are only 10-200 microns thick andwells 70 are generally filled with conductive viscous gel material orhydrogel material to within about 0.2 mm of the top of the dividingelements. In general, if low separators are used, the hydrogel may beomitted. However, in the preferred embodiment of the invention, thewells are at least partially filled by hydrogel or a similar material.

[0113] Hydrogel is available in both UV cured and heat curedcompositions. In either case a measured amount of uncured semi-liquidhydrogel is introduced into each well and the hydrogel is cured.Alternatively, the wells are filled with the uncured material and asqueegee which is pressed against the top of the divider elements with apredetermined force is moved across the top of the divider elements.This will result in the desired gap between the top of the hydrogel andthe top of the wells.

[0114] In an alternative embodiment of the invention, the hydrogelmaterial is replaced by a sponge material or similar supportive matriximpregnated with conductive viscous gel or the well is simply filledwith the conductive gel to the desired height.

[0115] During use of the probe, the probe is urged against the skinwhich is forced into the wells and contacts the hydrogel or alternativeconductive material. Optionally, a somewhat viscous conductive gel, suchas Lectron II Conductivity Gel (Pharmaceutical Innovations, Inc. Newark,N.J.), may be used to improve contact with the skin. In this case, thedividing elements will reduce the conduction between the cells such thatthe substantial independence of the individual measurements ismaintained. Alternatively, the conductive gel may be packaged togetherwith the probe, with the conductive gel filling the space between thetop of the hydrogel and the top of the wells. The use of a conductivegel is preferred since this allows for sliding movement of the probe andits easy positioning while it is urged against the skin. The separatorssubstantially prevent the conductive gel from creating a low conductancepath between adjoining sensing elements and also keep the hydrogelelements from touching each other when the probe is applied to the skinwith some pressure.

[0116] In a further preferred embodiment of the invention, the sensingelements are formed of a conductive foam or sponge material such assilicone rubber or other conductive rubber or other elastomerimpregnated with silver or other conductive material, as shown in FIG.5C. FIG. 5C shows the sensing elements without walls 66. Elements whichprotrude from the substrate as shown in FIG. 5C may achieve substantialelectrical isolation from one another by spacing them far enough apartso that do not contact each other in use or by coating their lateralsurfaces with insulating material such as polyethylene or other softnon-conductive plastic or rubber.

[0117] For relatively short rigid or compressible elements, it has beenfound that reducing the size of the sensing elements such that no morethan 70% (and preferably no more than 50%) of the area of the array iscovered is sufficient to reduce the “cross-talk” between adjoiningelements to an acceptable level.

[0118] If sufficiently good isolation is achieved between probe elementsby their spacing alone, then foam or other elements without hydrogel andwithout walls 66 may be provided. Sensing elements such as those shownin FIG. 5C conform and mate to uneven surfaces when pressed againsttissue.

[0119] Multi-element probe 62′, which is preferably used for only onepatient and then discarded, is preferably removably attached to a probeholder which preferably comprises a printed circuit board 80 having aplurality of contacts 82 corresponding to the contacts 74 on the back ofthe substrate, each PC board contact 82 being electrically connected toa corresponding contact 74 on the substrate. To facilitate alignment ofthe matching contacts, an alignment guide 90 is preferably provided onor adjacent to PC board 80 (FIG. 4). This guide may consist of a seriesof guide marks or may consist of a raised edge forming a well into oronto which the substrate is inserted. Conductors within PC board 80connect each of the contacts to one of the pins of connector 51, whichis preferably mounted on PC board 80.

[0120] Alternatively and preferably, as described below with respect toFIG. 6B, the guide may consist of two or more pins located on or near PCboard 80, which fit into matching holes in probe 62′.

[0121] Alternatively as shown in FIG. 5B, the back side of the embossingof substrate 68 is used as the guide for one or more protruding elements83 which are preferably mounted on PC board 80. Preferably a pluralityof protruding elements are provided to give good alignment of thesubstrate with the PC board. The elements may run along the periphery ofthe probe and form a frame-like structure as shown in FIG. 5B or may runbetween the elements or may take the form of x shaped protuberanceswhich match the shape of the embossing at the corners of the wells.

[0122] Protruding elements 83 may be formed of polycarbonate, acetate,PVC or other common inert plastic, or of a noncorrosive metal such asstainless steel.

[0123] A wire 84 is connected to each PC contact 82 and is alsoconnected to apparatus which provides voltages to and/or measuresvoltages and/or impedances at the individual sensing elements 64, asdescribed below.

[0124] In a preferred embodiment of the invention, conductive adhesivespots 86 preferably printed onto the back of the substrate are used toelectrically and mechanically connect contacts 74 with their respectivecontacts 82. Preferably a conductive adhesive such as Pressure SensitiveConductive Adhesive Model 102-32 (Creative Materials Inc.) is used.Alternatively, the adhesive used for printing the contacts/feed-throughsis a conducting adhesive and adhesive spots 86 may be omitted.Alternatively, pins, which protrude from the surface of PC board 80 andare connected to wires 84 pierce the substrate (which may be pre-bored)and contact the gel or hydrogel in the wells. A pin extending from thesubstrate may also be inserted into a matching socket in the PC board toform the electrical connection between the sensing element and the PCboard. Alternatively, the entire back side of the substrate can beadhered to the printed circuit board surface using an anisotropicallyconductive thin film adhesive which has a high conductivity betweencontacts 74 and 82 and which has a low conductivity resulting inpreferably many times higher resistance between adjoining contacts thanbetween matching contacts, in practice at least one hundred timesdifferent. An example of such adhesive is tape NO. 3707 by MMMCorporation, Minneapolis Minn. However, due to the difficulty ofapplying such material without trapped air bubbles, it may be preferablyto apply adhesive only to the contacts themselves. In practice a releaseliner of polyethylene, mylar or paper with a non-stick surface on oneside is provided on the lower side of the adhesive sheet. This linerprotects the adhesive layer prior to connection of the disposablemulti-element probe to the probe holder and is removed prior to theconnection of the probe to the holder.

[0125] Preferably, the impedance between contacts 82 and skin side ofthe conducting material in the wells should be less than 100 ohms at 1kHz and less than 400 ohms at 10 Hz.

[0126] Impedance between any pair of contacts 82, with the multi-elementprobe mounted should preferably be greater than 10 kohm at 1 kHz or 100kohm at 10 Hz.

[0127] Another suitable material for producing substrates is TYVEX(DuPont) substrate which is made from a tough woven polyolefin materialavailable in various thicknesses and porosities. If such material havinga suitable porosity is used, contacts 72 and 74 and feed-through 76 canbe formed by a single printing operation with conductive ink on one sideof the TYVEX sheet. Due to the porosity of the TYVEX, the ink willpenetrate to the other side of the TYVEX and form both contacts andfeed-through in one operation.

[0128] For probe 62 in the embodiment of FIG. 3A, substrate 68 isreplaced by a relatively rigid PC board which includes conducting wiresto attach each of electrical contacts 72 to one of the pins of connector51 (FIG. 3A) and the rest of the connecting structure of FIG. 5A may beomitted. It should be noted that the choice of using the structure ofFIGS. 3A or 3B (i.e., probes 62 or 62′) is an economic one depending onthe cost of manufacture of the probes. While probe 62 is structurallysimpler, the disposable portion of probe 62′ is believed to be lessexpensive to manufacture in large quantities. Since it is envisionedthat the probes will be used in large quantities and will preferably notbe reused, one or the other may be preferable.

[0129] The other side of the probe is also protected by a cover plate 88(FIGS. 5A and 5B) which is attached using any bio-compatible adhesive tothe outer edges of dividers 66 (FIG. 5A) and/or to the hydrogel, whichis preferably moderately tacky. In one preferred embodiment of theinvention, the inner surface of the cover plate 88 is provided with anelectrically conductive layer so that the impedance of each sensingelement from the outer surface of the hydrogel (or conductive gel) tocontact 82, can be measured using an external source. In addition, if aknown impedance is connected between the conductive layer and areference point or a source of voltage, the sensing elements can betested in a measurement mode similar to that in which they will finallybe used.

[0130] Alternatively, a film RC circuit or circuits may be printed onthe inner surface of plate 88 to simulate an actual impedance imagingsituation. Alternatively, plate 88 may be provided with contacts at eachsensing location, and circuitry which may simulate a plurality of actualimpedance imaging situations. Such circuitry may include external orintegral logic such as programmable logic arrays and may be configurableusing an external computer interface. The simulation may provide adistinct RC circuit for each sensing element or may provide a sequenceof different circuits to each sensing element to simulate the actualrange of measurements to be performed using the probe.

[0131]FIG. 5B shows a preferred embodiment of cover sheet 88 (indicatedon the drawing as 88′) and its mode of attachment to both themulti-element sensor and the PC board. In this embodiment amulti-element probe 62″ is optionally further attached to PC board 80 byan adhesive frame 210 which may be conductive or non-conductive, andwhich assists in preventing entry of water or gel under sensor 62″.Sensor 62″ is preferably further aligned to PC board 80 by one or moreholes 222 with one or more pins 204, which are permanently attached toPC board 80 or to a surface adjacent to PC board 80. While pin 204 isshown as being round, using rectangular, triangular, hexagonalpyramidical or other shapes provides additional alignment of the sensor.In general the upper portion of the pin should be curved for improvedelectrical contact as described below.

[0132] The upper exposed surface of pin 204 is conductive, preferablycurved and is preferably connected to a signal reference source by aconductor 202 in PC board 80. Cover sheet 88′ is made of a singleintegral sheet of easily deformable polyethylene, Mylar or othersuitable plastic. Cover sheet 88′ is preferably removably attached tothe upper side of multi-element probe 62″ by a continuous frame ofadhesive 225, which need not be conductive, but which seals around a lipwhere cover 88′ contacts probe 62″ to protect the quality and sterilityof array 230 and to maintain the moisture content of any medium fillingwells 70. Cover 88′ is coated on the side facing probe 62″ with aconductive layer 231, such as any of the various metallic coatings, forexample, aluminum or the thin film coating described above.

[0133] Cover 88′ is preferably formed after conductive coating, byembossing, vacuforming or other means, to have depressions 233 in thecover located over corresponding wells 70. The depressions areapproximately centered on the center of the wells and held a smalldistance “δ1” above the surface of the hydrogel or gel, by means ofrelatively high sidewalls 226 which are formed at the same time asdepressions 233. Furthermore, the surface of cover 88′ preferably has aconcave shape to match the rounded conductive contact surface of pin204, from which it is held at a distance “δ2″. Distances δ1 and δ2 areselected to minimize unintended physical contact between the conductiveinner surface of the cover, the contacts in the wells and pin 204, forexample, during storage and handling prior to use, which might causecorrosion over time due to electrochemical processes.

[0134] Distances δ1 and δ2 are also preferably selected so thatapplication of a nominal force (preferably about one kilogram) against aflat outer surface 232 of cover 88′, such as by a weighted flat plate,will establish contact between the inner coating 231 and the uppersurface of pin 204 and with the sensing elements or the gel in thewells.

[0135] By establishing this contact, the conductive inner surface 231 isconnected, on the one hand to signals source contact 202 and with eachsensing element. If the coating is a conductor, the sensing elements areall excited by the signal on line 202; if it is a thin film circuit, thecontact is via the thin film circuit. In either event, if line 202 isexcited by a signal, the signal will be transmitted to each of thesensing elements, either directly, or via a known impedance.

[0136] In either case, the multi-element array can be tested by thesystem and any residual impedance noted and corrected when the probe isused for imaging. If the residual impedance of a given sensing elementis out of a predetermined specification, or is too large to becompensated for, the multi-element probe will be rejected. Furthermore,the computer may be so configured that imaging may only take place afterdetermination of the contact impedance of the sensing elements or atleast of verification that the probe impedances are within apredetermined specification.

[0137] While pin 204 is shown as being higher than the top of the wells,the pin may be at the same height as the wells, or even below the wellswith the cover being shaped to provide a suitable distance “δ2″ asdescribed above.

[0138] In an alternative embodiment of the invention, the contactsurface corresponding to pin 204 is printed on or attached to thesurface holding the sensing elements, with contact to the PC board beingvia a through contact in substrate 68, as for the sensing elements.

[0139] In yet another embodiment of the invention, the conductivecontact surface associated with pin 204 is on the surface holding thesensing elements adjacent to pin 204. Pin 204 supports this surface andcontacts the contact surface via one, or preferably a plurality ofthrough contacts. Pin 204 is designed to match the contour of thecontact surface and preferably, by such matching, to provide additionalalignment of the probe on the PC board.

[0140] To avoid drying out of the Gel or other potential hazards oflimited shelf life, the quality of any of the aforementioned versions ofthe disposable electrode arrays can be assured by incorporating anidentification code, preferably including manufacturer and serial numberinformation and date of manufacture. In a preferred embodiment, theinformation is coded in a bar code printed on each disposable probe,which is packaged together with at least one other such probe (typically5-50 probes) in the same packet, which also has the same bar code. A barcode reader, interfaced with the system computer, reads themanufacturing information on the packet and each probe, checking fordate and compliance and permitting recording only for a number ofpatients equal to the number of probes in the packet.

[0141] In a preferred embodiment of the invention a bar code may beplaced on the individual disposable electrode arrays which can be readby a bar code reader installed in or under the PC board, for examplenear reference numeral 83 of FIG. 5B.

[0142] While the invention has been described in conjunction with thepreferred embodiment thereof, namely a generally flat, somewhat flexiblestructure, suitable for general use and for breast screening, othershapes, such as concave structures (e.g., brassiere cups) or the likemay be preferable, and in general the shape and configuration of thedetectors will depend on the actual area of the body to be measured. Forexample cylindrical arrays can be useful in certain situations, forexample in intra-rectal examinations of the prostate or colon or insidevessels. In this context, a probe according to the invention is alsouseful for measurements inside the body, for example gynecologicalmeasurements or measurements in the mouth, where the probe is insertedinto a body cavity and contacts the lining of the cavity, and probeshaving shapes which correspond either flexibly or rigidly to the surfacebeing measured can be used. For example, a multi-element probe inaccordance with the invention may be incorporated into or attached to alaparoscopic or endoscopic probe.

[0143] Furthermore, sterilized probes can be used in invasive proceduresin which the probe is placed against tissue exposed by incision. In thiscontext, the term “skin” or “tissue surface” as used herein includessuch cavity lining or exposed tissue surface.

[0144] In a preferred embodiment of the invention, PC board 80 and asmany elements as possible of probe 62′ (or the board of probe 62) aremade of transparent or translucent material, so as to provide at leastsome visibility of the underlying tissue during placement of probe 62.Those elements of the probe and conductors in the PC board, to theextent that they are opaque should be made as small as practical toprovide the largest possible view to a technician or clinician to aid inplacement of the probe. Furthermore, probe 62 is slidably displaceablewhen used with the above-mentioned conductive gel to permit moderatelateral adjustment of the probe position, to aid in placement, to ensuregood contact between each element and the tissue surface to be measured,and to enable the user to rapidly verify whether detected abnormalitiesare artifacts due to poor contact or are genuine objects, sinceartifacts remain stationary or disappear entirely when the probe ismoved while genuine objects just move in a direction opposite to thedirection of movement of the probe.

[0145] The general shape and size of the multi-element probe and thesize of the conductive sensing elements will depend on the size of thearea to be measured and on the desired resolution of the measurement.Probe matrix sizes of greater than 64×64 elements are envisioned forviewing large areas and probes which are as small as 2×8 elements can beuseful for measuring small areas. Element size is preferably between 2mm square and 8 mm square; however, larger sizes and especially smallersizes can be useful under certain circumstances. For the breast probe 62described above, 24×32 to 32×40 elements appear to be preferred matrixsizes.

[0146]FIG. 6A shows a perspective view of a hand held probe 100 inaccordance with a preferred embodiment of the invention. Probe 100preferably comprises two probe heads, a larger head 102 and a zoomsensor head 104. A handle 106 connects the sensor heads, housesswitching electronics and provides means for holding and positioning theprobes. Handle 106 also optionally incorporates a digital pointingdevice 105 such as a trackball, pressure sensitive button or other suchjoystick device. Incorporation of a pointing device on the probe enablesthe operator to control the system and input positional informationwhile keeping both hands on either the probe or patient. As describedbelow, the digital pointing device can be used to indicate the positionon the patient's body at which the image is taken.

[0147]FIG. 6B shows a partially expanded bottom view of probe 100 ofFIG. 6A, in accordance with a preferred embodiment of the invention.Where applicable, like parts of the probes throughout this disclosureare similarly numbered. Starting from the bottom of FIG. 6B, the tophalf of a housing 108A has a well 110 formed therein. A clear plasticwindow 112 is attached to the edge of well 110, and a printed circuit ona relatively transparent substrate, such as Kapton, designated byreference 80′ (to show its similarity to the corresponding unprimedelement of FIG. 5) is placed on window 112. A flexible print cable 114connects the contacts on printed circuit 62′ to acquisition electronics116. A cable 118 connects the acquisition electronics to the computer. Asecond similarly constructed, but much smaller zoom sensor probe head isattached to the other end of probe 100. Either of the larger or smallerheads may be used for imaging.

[0148] A lower half of housing 108B, encloses electronics 116 and print80′, whose face containing a series of contacts 82′, is availablethrough an opening 120 formed in the lower housing half 108B. A mountingframe 122 having two alignment pins 124 holds print 80′ in place.Mounting and connecting screws or other means have been omitted forsimplification.

[0149] A disposable multi-element probe 62′, similar to that of FIG. 5is preferably mounted on the mounting frame to complete the probe.

[0150]FIG. 7A is a perspective view of a fingertip probe 130 inaccordance with a preferred embodiment of the invention as mounted onthe finger 132 of a user. Probe 130 may be separate from or an integralpart of a disposable glove, such as those normally used for internalexaminations or external palpation. The fingertip probe is especiallyuseful for localizing malignant tumors or investigating palpable massesduring surgery or during internal examinations. For example, duringremoval of a tumor, it is sometimes difficult to determine the exactlocation or extent of a tumor. With the local impedance map provided bythe fingertip probe 130 and the simultaneous tactile information aboutthe issue contacted by the probe, the tumor can be located and itsextent determined during surgery. In a like fashion, palpable lumpsdetected during physical breast (or other) examination can be routinelychecked for impedance abnormality.

[0151]FIG. 7B shows a flexible probe array 140 which is shown asconforming to a breast being imaged. Probe array 140 comprises aplurality of sensing elements 141 which contact the tissue surface whichare formed on a flexible substrate. Also formed on the flexiblesubstrate are a plurality of printed conductors 142 which electricallyconnect the individual sensing elements 141 to conductive pads on theedge of the substrate. A cable connector 144 and cable 145 provide thefinal connection link from the sensing elements to a measurementapparatus. Alternatively, the flexible array may take a concave orconvex shape such as a cup (similar in shape to a bra cup) which fitsover and contacts the breast.

[0152] The flexible substrate is made of any thin inert flexible plasticor rubber, such as those mentioned above with respect to FIG. 5A. Array140 is sufficiently pliant that, with the assistance of viscous gel orconductive adhesive, the sensor pads are held in intimate contact withthe skin or other surface, conforming to its shape.

[0153]FIG. 8 shows an intra-operative paddle type probe 140 used, in asimilar manner as probe 130, for determining the position of anabnormality in accordance with a preferred embodiment of the invention.This probe generally includes an integral sensing array 143 on one sideof the paddle. Preferably, the paddle is made of substantiallytransparent material so that the physical position of the array may bedetermined and compared with the impedance map.

[0154]FIG. 9 shows a laparoscopic probe 150 in accordance with apreferred embodiment of the invention. Probe 150 may have a disposablesensing array 152 mounted on its side or the sensing array may beintegral with probe 150, which is disposable or sterilizable.

[0155] Multi-element probes, such as those shown in FIGS. 7, 8 and 9,are preferably disposable or sterilizable as they are generally are usedinside the patients body in the presence of body fluids. In suchsituations, there is generally no need or desire for a conductive gel inaddition to the probes themselves. Generally, printed sensing elements,such as those printed with silver-silver chloride ink, or sensingelements formed of conductive silicone, hydrogel or of a conductivesponge may be used. While in general it is desirable that the sensingelements on these multi-element probes be separated by physicalseparators 66 (as shown in FIG. 5), under some circumstances thephysical distance between the elements is sufficient and the separatorsmay be omitted.

[0156] When performing a needle biopsy, a physician generally relies ona number of indicators to guide the needle to the suspect region of thebody. These may include tactile feel, X-Ray or ultrasound studies orother external indicators. While such indicators generally give areasonable probability that the needle will, in fact take a sample fromthe correct place in the body, many clinicians do not rely on needlebiopsies because they may miss the tumor.

[0157]FIG. 10 shows a biopsy needle 154, in accordance with a preferredembodiment of the invention, which is used to improve the accuracy ofplacement of the needle. Biopsy needle 154 includes a series of sensingelements 156 spaced along the length of the probe. Leads (not shown)from each of these elements bring signals from the elements to adetection and computing system such as that described below. Elements156 may be continuous around the circumference, in which case theyindicate which portion of the needle is within the tumor to be biopsied.Alternatively, the electrodes may be circumferentially segmented (a leadbeing provided for each segment) so that information as to the directionof the tumor from the needle may be derived when the needle is notwithin the tumor. Such an impedance sensing biopsy needle can be used,under guidance by palpation, ultrasound, x-ray mammography or otherimage from other image modalities (preferably including impedanceimaging as described herein), taken during the biopsy or prior to thebiopsy to improve the accuracy of placement of the needle. Inparticular, the impedance image from the needle may be combined with theother images in a display. While this aspect of the invention has beendescribed using a biopsy needle, this aspect of the invention is alsoapplicable to positioning of any elongate object such as an other needle(such as a localizing needle), an endoscopic probe or a catheter.

[0158] Returning now to FIGS. 1-3 and referring additionally to FIGS.11-14, a number of applications of multi-element probes are shown. Itshould be understood that, while some of these applications may requireprobes in accordance with the invention, others of the applications mayalso be performed using other types of impedance probes.

[0159]FIG. 11A shows the use of the biopsy needle in FIG. 10 togetherwith an optional ultrasound imaging head in performing a biopsy. Abreast 160 having a suspected cyst or tumor 162 is to be biopsied byneedle 154. An ultrasound head 164 images the breast and the ultrasoundimage, after processing by an ultrasound processor 166 of standarddesign is shown on a video display 168. Of course, the ultrasound imagewill show the biopsy needle. The impedance readings from probe 154 areprocessed by an impedance processor 170 and are overlaid on theultrasound image of the biopsy needle in the display by a video displayprocessor 172.

[0160] In one display mode, the portions, as shown in FIG. 11B of theneedle which are within the tumor or cyst and which measure a differentimpedance from those outside the tumor, will be shown in a distinctivecolor to indicate the portion of the needle within the tumor or cyst. Ina second display mode, the impedance measured will be indicated by arange of colors. In yet a third embodiment of the invention, in whichcircumferentially segmented sensing elements are employed, the impedanceprocessor will calculate radial direction of the tumor from the needleand will display this information, for example, in the form of an arrowon the display.

[0161] The image sensing biopsy needle can also be used with one or moreimaging arrays (28, 30) such as those shown in FIG. 6 or FIG. 3B toimpedance image the region to be biopsied during the biopsy procedure.Alternatively, at least one of the arrays can be an imaging array of thenon-impedance type. In one preferred embodiment, shown in FIG. 11C, theneedle is inserted through an aperture (or one of a plurality ofapertures) 174 in a multi-element probe which is imaging the region. Theregion may, optionally, be simultaneously viewed from a different angle(for example at 90° from the probe with the aperture) with an otherimpedance imaging probe. In the case that both arrays 28 and 30 areimpedance imaging arrays, the biopsy needle or other elongate object caneither have impedance sensing or not, and the two images help direct itto the region. The probe with one or more apertures is sterile andpreferably disposable. This biopsy method is shown, very schematically,in FIG. 11C.

[0162] In an alternative preferred embodiment of the invention, only theperforated plate through which the needle or elongate object is passedis an imaging array. In this case the array through which the needlepasses give a two dimensional placement of the impedance abnormalitywhile an imaging or non-imaging impedance sensor on the needle gives anindication of when the needle has reached the region of impedanceabnormality, as described above.

[0163] Alternative guiding systems for frontal and lateral breast biopsyor for guiding an elongate element to a desired impedance region of thebody are shown in FIGS. 11D and 11E, respectively.

[0164]FIG. 11D shows a system for in which two relatively large platemulti-element probes 28, 30 are placed on opposite sides of the desiredtissue, shown as a breast 160 of a prone patient 161. Sensor arrayprobes 28 and 30 are held in position by positional controller 181 viarotatable mounts 191. A mount 198 positions a biopsy needle 199 withinthe opening between probe arrays 28 and 30, and is operative to adjustits height. A suspicious region 183 which is located at positions 184and 185 on arrays 28 and 30 respectively as described herein, whichinformation is supplied to a CPU 197, which determines the position ofthe suspicious region for controller 181. The controller then insertsthe needle into the suspicious region, for example, to take the biopsy.Biopsy needle 199 is preferably of the type shown in FIG. 10 to furtheraid in positioning of the needle. As indicated above, this is notrequired for some embodiments of the invention.

[0165] Alternatively, biopsy needle 199 may be inserted through holesformed between the elements of probes 28 and/or 30 as described above.Furthermore, while automatic insertion of the biopsy needle is shown inFIG. 11D, manual insertion and guidance based on impedance imagesprovided by the probes is also feasible.

[0166]FIG. 11E shows a system similar to that of FIG. 11D in which theimaging and biopsy needle insertion is from the side of the breast,rather than from the front. Operation of the method is identical to thatof FIG. 11D, except that an additional probe 29 may be provided forfurther localization of suspicious region 183. Alternatively, one or twoof the probes may be substituted by plates of inert material for holdingand positioning the breast.

[0167] It should be noted that while the breast has been used forillustrative purposes in FIGS. 11A through 11E, the method described isapplicable to other areas of the body, with necessary changes due to theparticular physiology being imaged.

[0168] It should be understood that one or more of the elements on theneedle may themselves be electrified to cause them to “light-up” on theimage. This electrification may be AC or DC may be the same or differentfrom the primary image stimulus, may have a single frequency or acomplex form and may be applied in a continuous or pulsed mode. If oneor more of the sensing elements is used in this manner, said elementsare preferably alternatively used to apply an electrification signal andto function as sensors, i.e., to sense signals from the primarystimulus.

[0169]FIG. 12 shows, very schematically, the intra-operative probe ofFIG. 8 combined with a video camera 256 to more effectively correlatethe impedance measurement with the placement of the probe on the body.An intra-operative probe 140 preferably having a number of opticallyvisible fiduciary marks 146 is placed on the suspect lesion or tissue Avideo camera 256 sequentially views the area without the probe and thesame area with the probe in place and displays a composite image on avideo display 258 after processing by a processor 260. Processor 260receives the impedance data from probe 140, determines the positions ofthe fiduciary marks from the video image and superimposes the impedanceimage on the video image, with or without the probe, which is displayedon display 258.

[0170]FIG. 13 shows a laparoscopic or endoscopic probe 250 used inconjunction with a fiber-optic illuminator/imager 252. In thisembodiment, the laparoscopic impedance probe, which is formed on aflexible, preferably extendible paddle, is viewed by theilluminator/imager which is preferably a video imager, which is wellknown in the art. Probe 250 can be either round or flat, depending onthe region to be imaged. When the imager views a suspicious lesion ortissue, probe 250 is extended to determine the impedance properties ofthe lesion. The combination of probe 250 and imager 252 may beincorporated in a catheter 254 or other invasive element appropriate tothe region of the body being investigated.

[0171] Optically visible fiduciary marks 253 on probe 250 are preferablyused to determine the position of probe 250 within the video image ofthe tissue seen by fiber-optic illuminator/imager 252, in a mannersimilar to that discussed above with respect to FIG. 12.

[0172] In a preferred embodiment of a system using any of the biopsyneedle, intra-operative probe, finger tip probe or other embodimentsdescribed above, an audible sound proportional to an impedance parametermeasured by the needle or other sensor in or on the body is generated bythe system computer. This feature may be useful in situations where theprobe is placed in locations which are difficult to access visually,such as suspected lesions during surgery. Such an audible sound couldinclude any kind of sound, such as a tone whose frequency isproportional to the measured parameter or similar use of beeps, clicks,musical notes, simulated voice or the like. This feature can also beused for non-surgical procedures such as rectal, vaginal or oralexaminations, or other examinations.

[0173]FIG. 16 shows methods useful for estimating the depth of a lesionand also for determining if a image contains a true lesion or anartifact.

[0174] A breast or other region 160 is imaged by a probe 270, forexample, the probe of FIGS. 1-3 or FIGS. 6A and 6B. The depth of a localimpedance deviation can be estimated by palpating the breast or otherregion by a finger 272 or a plunger 274. The displacement of the localdeviation on the image will be maximized when the palpation is at thesame level as the lesion. It should also be understood that, wherepalpation causes movement of the local deviation on the impedance image,this is an indication that the deviation is “real” and not an artifact.

[0175] In a similar manner, application of variable compression to theimaging probe will result in a variation of the distance from the probeto deviation under the probe. This distance variation will cause acorresponding variation in the size and intensity of the deviation, thushelping to verify that the deviation is not artifactal.

[0176] Alternatively or additionally, the probe can be moved along thesurface of the tissue without moving the tissue. In this case, surfaceeffects will have a tendency to either disappear or to move with theprobe (remain stationary in the image) while real anomalies will move,on the image, in the opposite direction from the movement of the probe.

[0177] Alternatively or additionally, the probe and the tissue can bemoved together without moving the underlying structure (such as thebones). Tissue lesions will remain relatively stationary in the imagewhile bone artifacts will move in the opposite direction.

[0178] In operation, a system according to the present inventionmeasures impedance between the individual sensing elements and somereference point (typically the signal source point) at some other placeon the body. Generally, in order to produce an interpretable impedanceimage, the sensing elements in the multi-element probe should detectdistortions in the electric field lines due solely to the presence of alocal impedance difference between embedded tissue of one type (forexample, a tumor) and surrounding tissue of another type (for example,normal adipose tissue).

[0179] To avoid distortion in the field lines, the reference point istypically placed far from the sensor array, all sensing elements are allat ground or virtual ground, and the current drawn by the elements ismeasured. Since the probe is at ground (an equipotential) the electricfield lines (and the current collected by the elements) areperpendicular to the surface of the multi-element probe. In principle,if there are no variations of impedance below the probe, each elementmeasures the integrated impedance below the element. This first orderassumption is used in the determination of the position and/or severityof a tumor, cyst or lesion. It is clear, however, that the multi-elementprobe covers only a portion of even the organ which is being imaged. Thearea outside the area of the probe is not at ground potential, causingthe field lines to bend out at the periphery of the probe, biasing theedge of the impedance image.

[0180] To reduce this effect, a conductive “guard ring” is providedaround the edge of the imaged area to draw in and straighten the fieldlines at the edge of the imaged area. This guard ring, if one isdesired, can consist of merely ignoring the, presumably distorted,currents drawn by the elements at (or near) the edge of the probe andignoring the measurements made by these elements. In general, while theuse of a guard ring reduces the edge effect at the edge of the field, itis still generally necessary to determine values for comparison ordetermination of polychromic values near the ring based only on pixelsnear the ring and not on the image as a whole.

[0181] Furthermore, to possibly reduce the baseline impedancecontributed to the local impedance image by tissue between the remotesignal source and the region near the probe, an additional referenceelectrode may be placed on the patient's body relatively near themulti-element probe. For example, if the source is placed at the arm ofthe patient and the breast is imaged from the front, a referenceelectrode for sensing a reference voltage can be placed at the front ofthe shoulder of the patient. The measured impedances are then reduced bythe impedance value of the reference electrode. Alternatively, theimpedance values of the elements of the multi-element probe are averagedto form a reference impedance, and the display of the impedance map iscorrected for this reference impedance.

[0182] One way to substantially avoid at least some of the above-mentioned problems is to use the apparatus shown in FIGS. 1-3. Asindicated above, the apparatus incorporates two probe heads 28 and 30.The breast to be imaged is placed between the probe heads and the breastis compressed by the heads (although generally to a lesser degree thanin X-Ray mammography) so that the breast forms a relatively flat volumeand fills the region between the probes. It should be noted that, if thecurrent is measured at each of the sensing elements in both probes, thentwo somewhat different images of the same region are generated.Avoidance of the problems also results when the two multi-element probesare not parallel as described above.

[0183] It should be noted that when used on breasts, the images producedby the pair of large, flat probes of FIG. 3 have the same geometricconfiguration as standard mammograms. Furthermore if used in the samecompression orientations, the impedance images can be directly comparedto the corresponding mammograms. In one preferred embodiment of theinvention, mammograms corresponding to the impedance images to be takenare digitized, using film scanning or other digitization means known inthe art, and entered into the system computer. If the mammogram isalready digital, such as may be provided by a digital mammogram, theimage file can be transferred from the mammogram.

[0184] The mammograms and impedance images can be overlaid or otherwisecombined to form a single image. Such an image could highlight thoseareas of the mammogram in which the impedance is particularly low orhigh. Such a combined image thus presents two independent readouts(impedance and radiographic density) of the same well defined anatomicalregion in a known geometric orientation, to facilitate interpretation,correlation with anatomy and localization.

[0185] It is well known that the resolution of objects in an impedanceimage is reduced with distance of the object from the probe. Thus, it ispossible to estimate the distance of the object from the two probesbased on the relative size of the same object on the two differentprobes. As indicated above, two opposing views of the breast may betaken. This would provide further localization of the object.

[0186] In one mode, the sensing elements of one probe are allelectronically floating while the elements of the other probe are at avirtual ground (inputs to sensing electronics), and a remote signalsource is used, as previously described. After an image is obtained fromthe one probe, the roles of the two probes are reversed to obtain animage from the other probe.

[0187] Alternatively, if all of the elements of one of the flat probesare electrified to the same voltage and the measuring probe is kept atvirtual ground, the currents drawn from and received by the elements ofboth probes form a two dimensional admittance image of the regionbetween the probes.

[0188] In a further preferred embodiment of the invention, one or a fewclosely spaced sensing elements on one of the probes is electrified, andthe others are left floating. This would cause a beam-like flow ofcurrent from the electrified elements to the other sensing elements onthe other probe. The object would disturb this flow causing impedancevariations which are strongest for those elements which are in the pathof the current disturbed by the object. If a number of such measurementsare made with, each with a different group of electrodes beingelectrified, then good information regarding the position of the objectcan be obtained.

[0189] In practice, as indicated above, orthogonal views of the breastare taken giving additional position information.

[0190] In preferred embodiments of the invention the breast is imaged ata plurality of frequencies and both the real and imaginary parts of theimpedance are calculated. The sensitivity of the detection of malignanttissue is a function of frequency, and, for a particular frequency, is afunction of the impedance measure or characteristic used for imaging,for example, real part of the impedance (or admittance), imaginary partof the impedance (or admittance), absolute value Of the impedance (oradmittance), phase of the impedance (or admittance), the capacitance orsome function of the impedance or of admittance components.

[0191] In a practical situation, an impedance measure should give themaximum contrast between a malignancy and non-malignant tissue. It istherefore desirable to determine the frequency or combination offrequencies which give maximum detectability and to determine itquickly. One method of determining the frequency is to perform sweptfrequency measurements and to use the frequency or combination offrequencies which results in the best contrast. Alternatively, a numberof images taken at relatively close frequencies can be used. It isbelieved that for many purposes, at least four samples should be takenin the range between and including 100 and 400 Hz and, preferably, atleast one or two additional images are taken at frequencies up to 1000Hz.

[0192] A second method is to use a pulsed excitation and Fourieranalysis to determine impedance over a range of frequencies. The optimumfrequency or frequencies determined from the swept or pulsed measurementare then used in a single or multiple frequency measurement. A pulseshape which has been found useful in this regard is a bi-polar squarepulse having equal positive and negative going pulses of 5-10millisecond duration and fast rise and fall times.

[0193] A number of measures of the impedance, as described below, havebeen found useful for comparing different areas of the image. Generally,it is useful to display a gray scale or pseudo-color representation ofthe values of the impedance measure, either on a linear scale or wherethe square of the impedance measure is displayed. Also useful is an“absorption scale” where the value of an impedance measure, v, isdisplayed as:

d(v)=(max−1)*(exp(v*(max−1)−1))/(e−1),

[0194] where max is the maximum normalized value of v. Generally, thedisplay is most useful when the measure is normalized, either bydivision or subtraction of the minimum or average value of the measurein the display or the estimated standard deviation or other measure ofvariance for the image.

[0195] Furthermore, the display may be automatically windowed to includeonly those values of the impedance measure actually in the image, or toinclude a relative window of selectable size about the average value ofthe impedance measure. The range of values to be displayed may also bedetermined using a baseline average value measured at a region remotefrom irregularities, i.e., remote from the nipple of the breast.Alternatively, the baseline average may be a predetermined average valueas measured for a large group of patients. Alternatively, a referenceregion on the image may be chosen by the user to determine the baselineaverage to be used for windowing.

[0196] While the display may show the exact measure for each pixel as isconventional, for example, in displays of nuclear medicine images, in apreferred embodiment of the invention the display is an interpolatedimage formed by quadratic or cubic spline interpolation of the impedancemeasure values. This type of display removes the annoying checkerboardeffect of the relatively low resolution impedance image without anysubstantial loss of spatial or contrast detail.

[0197] The measures of impedance which have been found useful forcomparing different areas of the image may be grouped as singlefrequency measures and polychromic measures.

[0198] Single frequency measures include the admittance, capacitance,conductance and phase of the admittance and its tangent. These measuresmay be measured at some predetermined frequency, at which thesensitivity is generally high, or at a frequency of high sensitivitydetermined by a preliminary swept or pulsed measurement. Cancertypically has significantly higher phase than the average surroundingtissue, with greatest difference at low frequencies such as 100 Hz, butoften significant up to 5 KHz.

[0199] Polychromic impedance measures are based on measurements at morethan one frequency, such as on a spectral curve based on fitting a setof capacitance (C) and conductance (G) values determined at a pluralityof frequencies using linear interpolation, quadratic interpolation,cubic spline, band limited Fourier coefficients, or other methods knownin the art.

[0200] One polychromic measure is a spectral width measure. For a givenpixel or region of interest the value of C parameter falls (and the Gparameter rises) with frequency. The spectral width of the spectrum isthe width to a given percentage fall in the C value as compared to thevalue at some low frequency, for example 100 Hz. If the parameter doesnot fall by the given percentage in the measured range it is assigned animpedance measure equal to the full measured bandwidth. Similarly, thespectral width of the G-spectrum is the width to a given rise in theG-Parameter compared to the value at some low frequency, for example 100Hz, or alternatively, the fall in G with decreasing frequency comparedto the value at some high frequency, for example 3000 Hz.

[0201] A second polychromic measure is a spectral quotient in which theimpedance measure is the ratio of the measured value of G or Cparameters at two preset frequencies, which may be user selected, orwhich may be selected based on the swept or pulsed measurementsdescribed above. This measure, as all of the others may be displayed ona per-pixel basis or on the basis of a region of interest of pixels,chosen by the user.

[0202] A third type of polychromic measure is based on a RelativeDifference Spectrum determination. In this measure, the capacitance orconductance for a given region of interest (or single pixel) is comparedto that of a reference region over the spectrum to determine a numericaldifference between the two as a function of frequency. The thus derivedRelative Difference Spectrum is then analyzed. For example, a spectralwidth measure as described above has been found to be a useful measureof abnormalities. Normally the width is measured where the relativedifference spectrum passes from positive to negative, i.e., where the Cor G is equal to that of the reference region. For capacitance, thisspectrum width is designated herein as the Frequency of CapacitanceCrossover (FCX). This measure has been found to be especially useful inclassification of tissue types as described below.

[0203] A fourth type of polychromic measure is based on a Relative RatioSpectrum determination. This is similar to the Relative DifferenceSpectrum, except that the ratio of the values between the reference areaand the region of interest is used. A spectral width measure can bedetermined for this spectrum in the same manner as for the Relativedifference Spectrum. Normally, the width is measured where the ratiois 1. This width is the same as the width of Relative DifferenceSpectrum at the zero (cross-over) point.

[0204] A fifth type of polychromic measures are the Positive andNegative Integrated Relative Difference for Capacitance and/orConductance abbreviated C (for capacitance) or G (for conductance) NIRDor PIRD. These values are calculated by adding up the negative (orpositive) deviations of the capacitance (or conductance) values in thearea of abnormality from those of a representative value (or range ofvalues) of the capacitance (or conductance) at the various measuredfrequencies. This representative value or range is determined from pixelvalues in the image selected to exclude exceptionally high or lowcapacitance (or conductance) values. The same pixel may have both aC-NIRD and a C-PIRD if its capacitance deviates positively from therepresentative value for some subset of the frequencies and negativelyfrom the representative value for a different subset of the frequencies.The C-NIRD, C-PIRD and G-NIRD measures have been found to be especiallyuseful for characterizing tissue type as described below.

[0205] A sixth polychromic measure is the integrated phase. For a givenpixel in the image, the phase is measured at a plurality of frequenciesin a desired frequency range, typically 100 to 5000 Hz. The integratedphase is the sum of the phase over a number of frequencies, typicallyabout 13 frequencies between 100 and 3200 Hz. Alternatively, integrationmay be performed using the trapezoidal rule or by integrating anotherfunctional fit to the sampled values in the desired frequency range.Cancer typically has significantly higher integrated phase. Theintegrated tangent of the phase is an alternative measure of thismeasure.

[0206] A seventh polychromic measure is the integrated phase difference.In a given image, the phase of each pixel is measured at each of aplurality of frequencies in a desired frequency range, typically 100 to5,000 Hz and the median or average phase determined for the image ateach frequency. In calculating the median or the average, the highestand lowest values are preferably excluded by using such methods as (1)including only pixels whose values lie within a specified range of thepixel histogram, such as only those between the 25 and 75 percentilephase values for the image. For each frequency, the median or averagefor the image is subtracted from the phase value for each pixel. Thisresults in a phase difference spectrum which is positive for frequencieswhere the pixel value is higher than average and negative where it islower. The sum of the phase differences is the integrated phasedifference (IPD), and the sum of all the positive phase differences isthe integrated positive phase difference. Both these measures aresignificantly higher for cancer than for normal surrounding tissues.

[0207] An eighth polychromic measure is the specific frequency. Thephase of each pixel is measured at each of a plurality of frequencies ina desired frequency range, typically 100 to 5000 Hz. The resultantspectrum is fitted to a piecewise linear function, a spline function ora functional fit as known in the art. The lowest frequency at which thephase reaches 45 degrees is defined as the Specific Frequency. SpecificFrequency is typically lower for cancer (range of 100 to 800 Hz) thanfor normal surrounding tissue (range of 1200 Hz to several kilohertz.The RC time constant evaluated at the specific frequency is also auseful related polychromic measure, being lower for cancer.

[0208] A ninth polychromic measure is the capacitance spectral slope,i.e., the derivative of the capacitance curve (or of the log capacitancecurve). as a function of frequency, evaluated at a given frequency. Thisis considered to be a polychromic measure, since its determinationrequires the measurement of the capacitance at more than one point.Capacitance Spectral slope in the range 100 to 5000 Hz is typicallynegative and typically has a higher absolute value in cancer vs. normalpixels, particularly at low Frequencies such as 100 to 500 Hz.

[0209] A tenth polychromic measure is the conductance spectral slope,the derivative of the conductance (or of the log conductance) evaluatedat a given frequency. Conductance Spectral slope in the range 100 to5000 Hz is typically positive and typically has a lower value in cancervs. normal pixels, particularly at low frequencies such as 100 to 500Hz.

[0210] The NIRD and PIRD measures may be defined in various ways. Forexample, the deviations from the representative value may be used in thecalculation only when they exceed some minimum value. The deviation maybe expressed as a the actual numerical deviation or more preferably as aratio or as a deviation normalized to some “standard” deviation of thecapacitance or conductance which is characteristic of normal tissue, asdefined below.

[0211] Preferably, the value representative of normal tissue is derivedby looking at pixel values representative of some proportion of thetotal number of pixels in an image. For example if a 8×8 image wereused, and the anomalous portion occupied less than 25% of the image, the16 pixels having each of the highest and the lowest values would not beconsidered. The representative value would then be, for example, themean value of capacitance or conductance of the remaining pixels and astandard deviation would be the range of pixel values among the 32pixels which are considered.

[0212] This determination is based on the practical consideration thatalmost always at least 50% of the pixels represent normal tissue. It isclear that many other measures of the representative value and of the“standard” deviation will be equally useful in the practice of theinvention and that such measures may be computed in many different ways.Furthermore the range of pixels which are considered “normal” may beadjusted depending on the type of tissue actually being measured. Forexample, for tissue having large areas with apparently high values, arange of pixel values such as, for example 20%-50% (instead of the25%-75% described above) may be more useful.

[0213] Another potentially useful polychromic parameter is the slope ofthe logarithm of the capacitance of a given pixel or region-as afunction of frequency. This curve generally has a shape which ispredominantly linear. Alternatively, the ratio of the slope of thecapacitance of the particular pixel to the slope of the capacitiverepresentative value may be useful.

[0214] Furthermore, it may be useful to consider, as an additionalpolychromic measure, the maximum of one of the other polychromicmeasures, for example, the capacitance, conductance, Relative DifferenceSpectrum, Relative Ratio Spectrum, etc.

[0215] In general, some pixels are excluded from the characterization.These would include “No-Contact” pixels having near zero conductance andcapacitance values and “Contact Artifactal Hot Spots” which are pixels,with elevated capacitance or conductance values, next to no contactpixels.

[0216] In impedance measurements of the breast in both men and women,normal breast tissue has a low capacitance and conductivity, except inthe nipples, which have a higher C and G values than the surroundingtissue with the maximum obtained at the lowest frequency recorded,typically 100 Hz. The nipple capacitance and conductance remains verymuch higher than the surrounding tissue up to about 1400 Hz for fertilepatients and up to about 2500 Hz for older patients (which is reduced to1400 Hz for older patients by estrogen replacement therapy). Thesefrequencies represent the normal range of spectral widths for theRelative and Difference Spectra. Tumors can be recognized by very high Cand G relative ratio or relative difference values at all frequenciesbelow 1000 Hz and moderate difference or ratio values for frequencies upto 2500 Hz or even higher.

[0217] Capacitance and conductance values are measured by comparing theamplitude and phase of the signal received by the sensing elements.Knowing both of these measures at the same points is useful to properclinical interpretation. For example, as illustrated below in FIG. 14, aregion of elevated conductivity and reduced capacitance (especially atrelatively low frequencies, most preferably less than 500 Hz, bygenerally below 2500 Hz and also below 10 kHz) is associated withbenign, but typically pre-cancerous atypical hyperplasia while, as shownin FIG. 15, cancer typically has both elevated capacitance andconductivity over, generally, a wide frequency range, as compared to thesurrounding tissue. Proper differential diagnosis is aided by having thefrequency samples be close enough together so that changes in theconductivity and capacitance in the low frequency range can be tracked.This also requires the display of both capacitance and conductance orthe use of an impedance measure which is based on an appropriatecombination of the two.

[0218] Methods for calculating C and G are given in the abovementionedU.S. Pat. Nos. 4,291,708 and 4,458,694, the disclosures of which areincorporated herein by reference. A preferred embodiment of theinvention takes advantage of the calibration capability inherent in theuse of cover plates as shown in FIGS. 5A and 5B. It can be shown that ifthe received waveform is sampled at a fixed spacing, 6, such that Nsamples are taken in each cycle, then the real and imaginary values ofthe impedance can be determined as:

G=Σ(g _(n)(V _((n+1/2N)) −V _(n)),

[0219] and

ωC=Σ(c _(n)(V _((n+1/2N)) −V _(n)),

[0220] where g_(n) and c_(n) are constants determined by a calibrationprocedure and V_(n) is the voltage measured at the nth sampling point(out of N). The first sample is taken at zero phase of the referencesignal.

[0221] One relatively easy way to determine the constants is to performa series of measurements when cover plate is in contact with the sensingelements as described above and a known impedance is placed between thetransmitter and the cover plate. Since N coefficients are required fordetermining g_(n) and c_(n) for each frequency, N values of admittanceand N measurements are required. For example, if N=4 (four samples percycle) four different measurements are taken and the sampled signalvalues are entered into the above equations to give N equations, whichare then solved for the values of the coefficients. The higher thenumber of samples, the greater the accuracy and noise immunity of thesystem, however, the calibration and computation times are increased.

[0222] Alternatively, fewer samples are taken and values for a number ofmeasurements are averaged, both in the calibration and clinicalmeasurements to reduce the effects of noise.

[0223] Artifactal abnormalities in the impedance image can be caused bysuch factors as poor surface contact or insufficient conductive couplingon some or all of the sensing elements, the presence of air bubblestrapped between probe and tissue and normal anatomical features such asbone or nipple.

[0224] Bubbles can be recognized by their typically lower C and G valuescompared to background, often immediately surrounded by pixels with muchhigher C and G. Bubbles can be verified and eliminated by removing theprobe from the skin and repositioning it, and or by applying additionalconductive coupling agent. Contact artifacts can be determined andaccounted for in real time by translating the probe and viewing theimage as described above. Artifacts either disappear or remain fixedwith respect to the pixels, while real tissue features move, on theimage, in a direction opposite from the motion of the probe.Additionally, as described above, if the tissue beneath the skin isphysically moved, while the probe and skeletal structure is kept fixed,only real tissue features will move. If the feature remains static, itis either a skin feature or bone.

[0225] If as described above, the probe and the tissue are movedtogether without moving the underlying structure (such as the bones).Tissue lesions and surface effects will remain relatively stationary inthe image while bone artifacts will move in the opposite direction, thusdistinguishing them from other impedance deviations.

[0226]FIG. 14 shows one example of a display, according to a preferredembodiment of the invention. In this display, capacitance andconductivity images at two positions on a breast are shown, togetherwith an indication of the positions on the breast at which these imageswere acquired.

[0227] In particular, as seen in FIG. 15, the display includes thecapability of displaying up to five sets of capacitance and conductanceimages in the five sets of smaller squares. These images are associatedwith probe areas indicated as numbers 1-5 on the breast image shown inthe display. In practice, the examiner manipulates a joystick or otherdigital pointing device, such as device 105 shown in FIG. 6A. Thisdevice is manipulated until a square is appropriately placed on thebreast image. The examiner then presses a button which causes a pair ofimpedance images to be stored and displayed on the screen in anappropriate square, and the indicated position to be displayed on thephysiological (breast) drawing. The small images are numbered from leftto right. Preferably, the examiner can scale the physiological image sothat the dimensions of the breast shown and the extent of the probearray are compatible. It should be understood that during the placementof the probe, real time images (acquired about once every 50-80 msec) ofthe capacitance and the conductance are shown, for example in the largesquares to the left of the display.

[0228]FIG. 14, which represents an actual imaging situation shows, inthe leftmost of the small images, a situation in which a small atypicalhyperplasia which was previously detected by other means. This positionshows an elevated conductivity and a very slightly reduced capacitance.In position 2, which is also shown in the two large squares to the rightof the display, a previously unsuspected area having acapacitance/conductance profile characteristic of atypical hyperplasiais detected.

[0229]FIG. 15 shows a study typical of multiple suspected sites ofcarcinoma (in positions 2 and 4). The images of position 4 are shown inenlarged format at the left of the image. In these sites, both thecapacitance and conductance are elevated with respect to theirsurroundings.

[0230] Alternatively, a composite image such as the image of the sum ofthe capacitance and conductance images, their product, their sum ortheir ratio can be displayed to give a similar indication of the type ofdetected anomaly. A color coded composite image can also be displayed,where, for example, the median value for each image would be black andwhere positive and negative values would have a particular color which,when combined would result in distinctive colors for suspect impedancedeviations.

[0231] The display shown in FIGS. 14 and 15 can be utilized to show aplurality of images of the same region at a plurality of frequencies.Alternatively or additionally, the display can be utilized to show aplurality of different polychromic measures of the same region. Inaddition, using, for example, the fact, as described below with anexample, that a plurality of such measures can be useful in identifyingtissue type more accurately than can a single measure, the display mayinclude, inter alia, an image in which portions of the image isidentified by tissue type. For such an image, for example, the color ofportions of the map could represent the type of tissue and thebrightness the certainty of the identification. The type identificationand certainty would depend on the probability that a particular “mix” ofvalues of the polychromic measures are associated with a particulartissue type and that not all measures are always within the specifiedrange for any particular tissue type. In conjunction with the display ofsuch a map the individual polychromic measures may be displayed eithertogether or in sequence to make the determination of the tissue typemore certain.

[0232] One type of display of multiple polychromic images is to use apseudo color image of two or three colors, each of which represents oneof the measures. When a measure for a portion of the image meets thecriteria for a given tissue type it is displayed in its assigned color.When two or more such criteria are met a different color is displayed,depending on which of the criteria are met.

[0233] Another type of display shows the values of the measures asiso-contours of varying brightness of a color assigned to the measure.The conjunction of isocontour lines characteristic of a given tissuetype may then be recognized from isocontours.

[0234] Alternatively or additionally, the image can be a pseudo 3-Dimage wherein each of the measures is delineated as a wire screen of agiven color. This allows for the visualization of more than one measureat the same time.

[0235] Alternatively, a map of immitance, or the real or imaginary partthereof is overlaid with indications, based on polychromic measures ofthe tissue type involved, as for example by color coding, by arrows withassociated legends or by other means to alert the operator to suspectedsites of tissue of specific types. Such measures may be calculatedautomatically or in response to a query from the operator in respect toan area of the image of which he is suspicious.

[0236] It has been found that certain immitance measures andcombinations of measures are characteristic of certain types of normaland abnormal tissue. In one example of the method four of thepolychromic measures described above can be utilized separately or, moreparticularly, in combination to indicate the presence of certain normalor abnormal tissue. These four measures are CFX, G-PIRD, C-PIRD andC-NIRD measure. Other combinations of polychromic measures are alsouseful in indicating tissue type.

[0237] It has been found that normal tissue, as expected, has low orzero values of all of the measures. Nipples and-the infra-mammary ridgehave a very high value of G-PIRD and CPIRD together with zero to lowvalue of CFX and no G-NIRD. Ribs and the costo-chondral junction havelow values of CPIRD and CFX, moderate to high values of G-PIRD and lowvalues of C-NIRD. Typical benign hyperplasia has a moderate to highvalue of C-NIRD and G-PIRD, a high value of CFX and no C-PIRD, whileprecancerous atypical hyperplasia has values in a range similar to thatof typical hyperplasia for C-NIRD, and G-PIRD but has a moderate valueof CFX and C-PIRD. This allows precancerous atypical hyperplasia to bedifferentiated from benign hyperplasia. Furthermore, cancerous tumorsappear to be characterized by medium to high values of C-PIRD and CFX,high values of G-PIRD and low values C-NIRD. Some tumors, especiallythose with very high C-PIRD have no CNIRD.

[0238] The four measures, C-PIRD, C-NIRD, G-PIRD and CFX, form a fourdimensional space in which each set of measurements in designated by asingle point. In order to represent such a space on paper two orthogonalprojections of the four dimensional space are required. One such set oforthogonal projections is shown in FIGS. 18A and 18B. While theseprojections fully describe all four measures, they plot the measures inpairs only. Presenting the regions of the space which are characterizedby the various tissue types in a single drawing is possible since all ofthe measures have only positive (or zero) values. Since only positivevalues of the measures are allowed it is possible to combine these twoorthogonal projections, as in FIG. 18C, into a single projection inwhich each of the axes represents a positive value of one of themeasures. FIG. 18C shows the information in a redundant manner (i.e., itactually shows two orthogonal projections), however, it is useful sinceit shows all combinations of the various measures on a single figure.

[0239] It will be noted from FIGS. 18A-C and from the above discussionthat there is some overlap between nipples (and Infra-mammary ridge) andtumors and also between ribs (and costo-chondral junction) and tumors.Where ambiguity does exist (i.e., in the relatively small overlap areasshown in FIG. 18C) the distinction can generally be made based on theanatomy of the portion of the patient being imaged. Thus, an ambiguoustumor/nipple far from the nipple would be classified as a tumor and atumor/rib far from the ribs would be classified as a tumor. Where theanatomy does not allow for a clear determination, such as for example atumor which is close to the nipple, an additional view and/or adifferent breast position, palpation or other methods of separating theanomaly from the normal tissue will generally remove the ambiguity.

[0240] While a particular impedance imaging system has been described asthe basis for determining the type of tissue underlying the anomalies(and causing them) The method is also believed to be generally useful intissue type determination using other types of impedance imaging systemsand also in situations where no image is generated.

[0241] For example, the method is also potentially useful to determinetissue types in situations where either a single impedance probe is usedor where the image is small and only anomalous areas are imaged. Inthese cases the comparison for determining the measures is made betweenthe values of capacitance or conductance measured for the anomalousregion as compared to the capacitance or conductance measured for anearby region known to be normal.

[0242] The method is also useful for determining the type of tissuewhich is pierced by a biopsy needle or contacted directly by a probesuch as the finger probe of FIG. 7A of the invasive probes of FIGS.8-10. In these cases a comparison may be made between values at thetissue to be characterized and other “normal” tissue.

[0243]FIGS. 17A and 17B show a block diagram of a preferred embodimentof a system 200 which incorporates a number of multi-element probes. Itshould be understood that the exact design of system for impedanceimaging will depend on the types of probes attached to the system andthe exact imaging modalities (as described above) which are used.

[0244] As shown in FIGS. 17A and 17B the preferred system canincorporate biopsy needle probe 154, two plate probes 28, 30 such asthose shown in FIGS. 1-3, scan zoom probe 100 such as that shown in FIG.6A, conformal probe 139 such as that shown in FIG. 7B, a bra-cup probe,finger/glove probe 130 such as that shown in FIG. 7A, laparoscopic probe150 such as that shown in FIG. 9 or an intra-operative probe 140 asshown in FIG. 8. Furthermore, when three probes are used as in FIG. 11E,provision is made for attachment of a third plate probe. The position ofthe plate and needle probes is controlled by controller 181 as describedin respect to FIG. 11D.

[0245] The probes as connected via a series of connectors, indicated byreference numeral 302 to a selection switch 304 which chooses one ormore of the probes in response to a command from a DSP processor 306.Selection switch 304 switches the outputs of the probes, namely thesignals detected at the sensing elements of the probes (or amplifiedversions of these signals) to a set of 64 amplifiers 308, one amplifierbeing provided for each sensing element. For those probes, such as thelarge plate probes, which have more than 64 sensing elements, theselection switch will (1) sequentially switch groups of 64 sensingelements to amplifier set 308, (2) choose a subset of sensing elementson a coarser grid than the actual array by skipping some elements, asfor example every second element, (3) sum signals from adjacent elementsto give a new element array of lower resolution and/or (4) choose only aportion of the probe for measurement or viewing. All of these switchingactivities and decisions are communicated to the switch by DSP processor306 which acts on command from a CPU 312. The output of the amplifiersis passed to a multiplexer 307 where the signals are serialized prior toconversion to digital form by a, preferably 12-bit, A/D convertor 310. Aprogrammable gain amplifier 309, preferably providing a gain which isdependent on the amplitude of the signals, is optionally provided tomatch the signal to the range of the A/D convertor. The output of A/D310 is sent to the DSP for processing as described above. In a preferredembodiment of the invention DSP 306 is based on a Motorola MC 68332microprocessor.

[0246] While 64 amplifiers has been chosen for convenience and lowercost, any number of amplifiers can be used.

[0247] The DSP calculates the impedance results and send the results toCPU 312 for display on a graphic data display 16, printing on a printer18 or other output signals generation as described above by a lightindicator 314 or a sound indicator 316.

[0248] Alternatively, the DSP directs signal sampling and averagestogether the samples or pre-processes them, sending the averaged orpre-processed samples to CPU 312, which then performs the impedancecalculations.

[0249] The CPU may also receive images from video camera 256, forexample, when used with an intra-operative probe, from an endoscopicoptics and camera system 320, for example when the camera views theouter surface of the laparoscopic probe or from an ultra sound imager322, for example, in biopsy performance as shown in FIGS. 11A and 11B.When an image is acquired from one of these cameras a frame grabber 324is preferably provided for buffering the camera from the CPU. Asdescribed above, the CPU combines these images with the impedance imagesprovided by one or more probes for display or other indication to theoperator.

[0250]FIG. 15 also shows a programmable reference signal generator 326which receives control and timing signals from the DSP. The referencesignal generator generates excitation signals which are generallysupplied, during impedance imaging, to reference probe 13, which, asdescribed above, is placed at a point (or at more than one point) on thebody remote from the region of impedance measurement. Signal generator312 may produce a sinusoidal waveform, pulses or spikes of variousshapes (including a bipolar square shape) or complex polychromicwaveforms combining desired excitation frequencies. Appropriateimpedance calculations, in DSP 306 or in CPU 312, are implemented inaccordance with the waveform of the excitation.

[0251] Where a breast is imaged and one of the two plates is used as thesource of excitation, as described above, the output of signal generatoris sent to the exciting plate (signal paths not shown for simplicity). Acurrent overload sensor 330 is preferably provided after the signalgenerator to avoid overloads caused by short circuits between thereference probe and the imaging probe or ground.

[0252] Also shown on FIG. 17A is an internal calibration reference 332which is preferably used for internal calibration of the system and fortesting and calibration of the probes.

[0253] For internal testing and calibration, calibration reference 232receives the signals generated by the programmable reference signalsgenerator as passed to the selection switch, in series with an internaladmittance in the calibration reference, as selected by the DSPprocessor. The DSP processor computes the admittance from signalsreceived from the A/D convertor and compares the computed admittancewith the actual admittance provided by internal calibration reference332. This comparison can be provide an indication that the systemrequires adjustment or repair or can be used to calibrate the system.

[0254] Similarly, the output of calibration reference 332 may beprovided to probe cover 88 for calibration and quality assurance of aplate or scan probe as described above. Under this situation, the DSPinstructs selection switch 304 to choose the input from the respectiveprobe.

[0255] Also provided is a user interface 334 such as a keyboard, mouse,joystick or combinations thereof, to allow the operator to enterpositional information via the screen and to choose from among theprobes provided and from the many options of calculation, display, etc.

[0256] Although described together as the preferred embodiment of theinvention, it is not necessary to use the probes of the invention, themethods of calculation of impedance and impedance characteristics of theinvention and the preferred apparatus of the invention together. Whileit is presently preferred that they be used together they may each beused with probes, calculation methods and apparatus for impedanceimaging as applicable and as available.

[0257] Certain aspects of the invention have been described with respectto a biopsy needle or with respect to placement of such a needle. Itshould be understood that such description and aspects of the inventionare equally applicable to positioning needles, catheters, endoscopes,etc.

[0258] Although various embodiments, forms and modifications have beenshown, described and illustrated above in some detail in accordance withthe invention, it will be understood that the descriptions andillustrations are by way of example, and that the invention is notlimited thereto but encompasses all variations, combinations andalternatives falling within the scope of the claims which follow:

1. Apparatus for aiding in the identification of tissue type for an anomalous tissue in an impedance image comprising: means for providing a polychromic immitance map of a portion of the body; means for determining a plurality of polychromic measures of an anomalous region of the immitance image; and a display which displays an indication based on said plurality of polychromic measures.
 2. Apparatus according to claim 1 including means for providing a map of said polychromic measures and wherein said indication includes a display of a plurality of said maps.
 3. Apparatus according to claim 2 wherein said display includes an overlay of maps of said polychromic measures.
 4. Apparatus according to claim 3 and including means for matching the values of the plurality of measures with predetermined values of the measures to identify the tissue type of the anomalous tissue.
 5. Apparatus according to claim 4 wherein the values of the measures are normalized values.
 6. Apparatus according to claim 4 wherein the indication is the display of a map of said determined tissue type.
 7. Apparatus for determining a tissue type for an anomalous tissue comprising: means for determining a plurality of polychromic measures of the anomalous tissue; and means for matching the values of the plurality of measures with predetermined values of the measures to identify the tissue type of the anomalous tissue.
 8. Apparatus according to claim 7 wherein the values of the measures are normalized values.
 9. Apparatus according to claim 7 wherein one of the polychromic measures is derived from the frequency at which the capacitance spectrum of the anomaly crosses a capacitance spectrum of typical nonanomolous regions.
 10. Apparatus according to claim 7 wherein one of the polychromic measures is derived from the integrated deviation of the capacitance or conductance of the anomaly from that of typical nonanomolous regions.
 11. Apparatus according to claim 10 wherein one of the polychromic measures is derived from the sum, over a plurality of frequencies, of the positive deviations of the capacitance of the anomaly from that of typical nonanomolous regions.
 12. Apparatus according to claim 10 wherein one of the polychromic measures is derived from the sum, over a plurality of frequencies, of the negative deviations of the capacitance of the anomaly from that of typical nonanomolous regions.
 13. Apparatus according to claim 10 wherein one of the polychromic measures is derived from the sum, over a plurality of frequencies, of the positive deviations of the conductance of the anomaly from that of typical nonanomolous regions.
 14. Apparatus according to claim 7 wherein one of the measures is the integral of the phase or the sum of phase values over a range of frequencies.
 15. Apparatus according to claim 7 wherein one of the measures is the difference between the integral of the difference between the phase at a point and the mean or median value of the phase in the image, over a range of frequencies.
 16. Apparatus according to claim 7 wherein one of the measures is the derivative of the capacitance curve or its logarithm as a function of frequency, evaluated at a given frequency.
 17. Apparatus according to claim 7 wherein one of the measures is the derivative of the conductance curve or its logarithm as a function of frequency, evaluated at a given frequency.
 18. Apparatus according to claim 7 wherein one of the measures is a frequency at which the phase of the impedance reaches a specified value.
 19. Apparatus according to claim 16 wherein the specified value is 45 degrees.
 20. A method of determining a tissue type for tissue in an anomalous region in an immitance image, comprising: determining a plurality of polychromic measures of said anomalous region; and matching the values of the plurality of measures with predetermined values to identify the tissue type of the anomalous region.
 21. A method of determining a tissue type for an anomalous tissue: determining a plurality of polychromic measures of the anomalous tissue; matching the values of the plurality of measures with predetermined values to identify the tissue type of the anomalous tissue.
 22. A method according to claim 21 wherein one of the polychromic measures is derived from the frequency at which the capacitance spectrum of the anomaly crosses a capacitance spectrum of typical nonanomolous regions.
 23. A method according to any of claim 21 wherein one of the polychromic measures is derived from the integrated deviation of the capacitance or conductance of the anomaly from that of typical nonanomolous regions.
 24. A method according to claim 23 wherein one of the polychromic measures is derived from the sum, over a plurality of frequencies, of the positive deviations of the capacitance of the anomaly from that of typical nonanomolous regions.
 25. A method according to claim 23 wherein one of the polychromic measures is derived from the sum, over a plurality of frequencies, of the negative deviations of the capacitance of the anomaly from that of typical nonanomolous regions.
 26. A method according to claim 23 wherein one of the polychromic measures is derived from the sum, over a plurality of frequencies, of the positive deviations of the conductance of the anomaly from that of typical nonanomolous regions.
 27. A method according to claim 21 wherein one of the measures is the integral of the phase or the sum of phase values over a range of frequencies.
 28. A method according to claim 21 wherein one of the measures is the difference between the integral of the difference between the phase at a point and the mean or median value of the phase in the image, over a range of frequencies.
 29. A method according to claim 21 wherein one of the measures is the derivative of the capacitance curve or its logarithm as a function of frequency, evaluated at a given frequency.
 30. A method according to claim 21 wherein one of the measures is the derivative of the conductance curve or its logarithm as a function of frequency, evaluated at a given frequency.
 31. A method according to claim 21 wherein one of the measures is a frequency at which the phase of the impedance reaches a specified value.
 32. A method according to claim 31 wherein the specified value is 45 degrees.
 33. A method according to claim 21 wherein the values of the measures are normalized values. 